Cholecystokinin-B/gastrin receptors enhance wound healing in the rat gastric mucosa
Adrian Schmassmann, Jean Claude Reubi
Adrian Schmassmann, Jean Claude Reubi
Published October 15, 2000
Citation Information: J Clin Invest. 2000;106(8):1021-1029. https://doi.org/10.1172/JCI8115.
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Article

Cholecystokinin-B/gastrin receptors enhance wound healing in the rat gastric mucosa

Abstract

Although physiological functions of the CCK-B/gastrin receptor are well explored, little is known about its role during healing. Here, we evaluated the role of this receptor in the rat oxyntic mucosa following the introduction of a cryoulcer. In this model, we located and quantified CCK-B/gastrin receptors by reverse transcriptase PCR and receptor autoradiography. Rats with cryoulcers were treated with placebo, omeprazole, the CCK-B/gastrin receptor antagonist YF-476, omeprazole plus YF-476, gastrin-17, and gastrin 17 plus YF-476. During wound healing, CCK-B/gastrin receptors were specifically expressed and localized to the regenerative mucosal ulcer margin. This high expression was limited in time, and the pattern of expression of CCK-B/gastrin receptors correlated closely with the proliferative activity of the regenerative mucosa. Functionally, omeprazole and gastrin-17 caused profound hypergastrinemia, increased cell proliferation in the mucosal ulcer margin and accelerated the late ulcer healing phase. These effects were completely reversed by cotherapy with YF-476. These in vivo and vitro data suggest that CCK-B/gastrin receptors in regenerative rat gastric oxyntic mucosa enhance trophic effects during wound healing.

Authors

Adrian Schmassmann, Jean Claude Reubi

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(a) 125I-CCK–specific binding in regenerative mucosa during healing. Whe...
(a) 125I-CCK–specific binding in regenerative mucosa during healing. Whereas labeling was uniform in the repair zone between days 3 and 8, two zones with different densities for the CCK-BR were detected on days 15 and 22. On days 15 and 22, a proliferative zone in the center of the healing process showed high specific binding, whereas the transitional zone located between the proliferative zone and the normal mucosa showed low specific binding. No or minimal significant binding was detected in the mucosal scar on days 29, 56, and 84 after ulcer induction. Data are expressed as the means ± SEM. (b) Typical displacement experiment of 125I-CCK for the CCK-BR in the repair zone on day 8. Tissue sections were incubated with 45 pM 125I-CCK and increasing concentrations of unlabeled, sulfated CCK-8, gastrin, YF-476, and L-364,718. The CCK-BR selective antagonist YF-476 displaces the ligand with a similar high affinity such as CCK-8 or gastrin. In contrast, the CCK-AR–selective antagonist L-364,718 displaces the ligand with low affinity only.